crossing96/oncoscreening huggingface dataset:
Urinary diversions for benign and oncologic indications: what did we learn about short term complications in the last 24 months?	PURPOSE OF REVIEW: Urinary diversion (UD) with or without cystectomy is a procedure with high short term complication rates. In this review, we summarize the most relevant findings of the last 2 years. RECENT FINDINGS: The use of a prophylactic mesh decreases the risk of parastomal hernia after ileal conduit (IC) surgery without adding mesh-related complications according to a recent randomized multicentre trial. Robot-assisted surgery is increasingly applied for UD and is evolving from extra- to intra-corporeal reconstruction in both continent and incontinent diversions, but there is still a need for appropriately designed studies assessing both short- and long-term complications. Promising techniques to decrease ureterointestinal stricture rates have been reported from small series, such as retrosigmoid placement of the proximal IC to avoid transpositioning of the left ureter, or in robot-assisted surgery the use of indocyanine green with near-infrared light to improve visualisation of distal ureteral viability. SUMMARY: Most recent reports derive from observational data. Appropriate randomized studies are warranted for the evaluation of new techniques to be implemented in a surgical area that still is associated with high complication rates.	bladder
A Case Report of Phenobarbital for Proportionate Sedation to Control Refractory Symptoms at the End of Life in an Opioid Tolerant Patient.	End of life (EoL) and refractory symptom management is a growing clinical topic and there is minimal literature to support effective treatment strategies, especially in individuals with a substance use disorder or opioids and/or benzodiazepine tolerance. We report the successful use of phenobarbital for proportionate EoL sedation in a 57-year-old man with opioid use disorder (heroin) and metastatic urothelial carcinoma presenting to an acute care hospital with intractable back pain related to bone metastases. During his hospitalization, his daily opioid requirement exceeded 1 gram of morphine equivalent daily dose (MEDD) with suboptimal pain control. The patient's clinical course was complicated by active heroin withdrawal, psychosocial suffering, and disease progression. Despite use of high-dose opioids and benzodiazepines, pain and anxiety were poorly controlled. After an acute medical decompensation, a goals of care discussion was held with his family and a determination with informed consent was made to change patient status to do not attempt resuscitation and proportionate sedation with phenobarbital was initiated to target refractory pain and agitation. Phenobarbital was continued for approximately 15 hours before patient peacefully died. Findings from this case report demonstrate the successful use of phenobarbital in opioid use disorder and benzodiazepine tolerance with intractable pain.	bladder
Combination Therapy With Immune Checkpoint Inhibitors in Urothelial Carcinoma: Current Data and Future Outlook.	Bladder cancer is the sixth most common cancer in the United States, with an estimated 81,400 new cases in 2020. Although bladder cancer has 4 stages, for systemic treatment we recognize 3 clinical stages: non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and locally advanced/metastatic urothelial carcinoma (mUC). Approximately 70% to 80% of patients present with NMIBC at diagnosis and have an excellent 5-year overall survival (OS) of 69.2% to 95.8%.1 About 10% to 15% of patients present with MIBC at the time of diagnosis and have about a 50% chance of progressing to metastatic disease.2 mUC accounts for 10% to 15% of all bladder cancers at diagnosis, with a 5-year OS for patients of fewer than 10% with platinum-based chemotherapy.	bladder
Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.	Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.	bladder
Somatic-Type Yolk Sac Tumor Arising as a Predominant Component of Bladder Urothelial Carcinoma.	Germ cell differentiation has been described in association with somatic tumors arising from several organ systems; rare cases arising from urothelium have been reported. Here we present a 62-year-old male with a remote history of lung cancer, a left adrenal gland mass, and a 5.6 cm left bladder wall mass; cystoscopy demonstrated a large papillary mass on the left anterior bladder wall. A transurethral resection specimen was sent for review in consultation and showed extensive papillary structures with thin fibrovascular cores lined by neoplastic cells with clear cytoplasm. These neoplastic cells were diffusely positive for pancytokeratin, CDX2 (caudal-type homebox 2), SALL4 (sal-like transcription factor 4), glypican-3, AFP (alpha-fetoprotein), while negative for PAX-8 (paired box gene 8), NKX3.1 (NK3 homeobox 1), PSA (prostate specific antigen), TTF-1 (thyroid transcription factor 1), Napsin A, inhibin, and OCT4 (octamer-binding transcription factor 4). Conventional urothelial conventional carcinoma and focal squamous differentiation were also identified as minor components. Urothelial carcinoma was focally positive for GATA3 (GATA-binding protein 3) and p63; SALL4 and glypican-3 were negative. Overall findings supported a yolk sac tumor with a smaller component of squamous cell carcinoma (<1%). Subsequent cystectomy showed similar morphologic features and immunoprofile in addition to foci of urothelial carcinoma and urothelial carcinoma in situ. No chromosome 12p abnormalities were identified by fluorescent in-situ hybridization study. A diagnosis of yolk sac tumor derived from urothelial carcinoma was made. Yolk sac tumor should be considered in the differential diagnosis of a high-grade urothelial carcinoma, particularly when glandular or other unusual architectural patterns are present. A somatic origin with underlying genomic instability similar to what has been described in the uterus and ovaries is suggested.	bladder
[Long-term results of radical surgery treatment of patients with bladder cancer].	PURPOSE: To investigate long-term results after radical cystectomy in patients with bladder cancer. MATERIALS AND METHODS: Since 1997 to 2020 yy. we have performed 404 radical cystectomy with different methods of derivation for patients with bladder cancer in our clinic. There were 342 (86,4%) men and 62 (13,6%) women. Laboratory study, ultrasound, X-ray, CT. MRI investigations were performed in all patients. RESULTS: Mortality rate was 2,9%. Early and late postoperative complications have occurred in 136 (33,6%) and 98 (41,8%) cases, respectively. Local recurrence has occurred in 33 (8,5%) patients. 10-years overall and cancer-specific survival were 43,4% and 47,2%, respectively. In lymph-negative patients 2-years and 5-years overall survival were 81,2% and 67,2%, respectively. In lymph positive patients 2-years and 5-years overall survival were 46,9% and 13,9%, respectively. In lymph-negative patients 2-years and 5-years cancer-specific survival were 83,6% and 70,7%, respectively. In lymph positive patients 2-years and 5-years cancer-specific survival were 51,0% and 15,1%, respectively. Overall and cancer -specific survival decreased according to increasing pT-stage and histopathologic grade. CONCLUSIONS: pT-stage (pT), lymp nodes status (pN), histopathologic grade ( pG) have a significant independent influence on overall and cancer-specific survival of bladder cancer patients after radical cystectomy.	bladder
The Association of Cell Surface Fibromodulin Expression and Bladder Carcinoma.	BACKGROUND: Fibromodulin (FMOD) is a secretory protein which is considered a major component of extracellular matrix. Its dysregulation in different types of cancer implies it as a promising target for cancer therapy. Within the scope of its rather wide expression in different tumors, we studied expression of FMOD and effect of anti-FMOD antibody in bladder cancer cells in order to identify new target for diagnostic and therapeutic interventions. We report here for the first time the expression of FMOD in bladder cancer cell lines in comparison to the normal cell line and tissues. METHODS: A peptide-based produced anti-FMOD murine monoclonal antibody (mAb) (clone 2C2-A1) was applied for evaluation of FMOD expression in bladder cancer and normal tissues by immunohistochemistry (IHC) staining. Furthermore, the expression of FMOD was examined in human bladder cell lines, 5637 and EJ138, as well as a non-cancerous human cell line, human fetal foreskin fibroblast (HFFF), by immunocytochemistry (ICC) and flow cytometry. The apoptosis induction of anti-FMOD mAb was also evaluated in bladder cancer cells. RESULTS: IHC and ICC analyses revealed that the qualitative expression of FMOD in bladder cancer tissues and cell lines is higher than in normal tissues and cell lines. Flow cytometry analyses revealed that 2C2-A1 mAb could recognize FMOD expression in 84.05 ± 1.85%, 46.1 ± .4% , and 2.56 ± 1.26% of 5637, EJ138, and HFFF cells, respectively. An effective apoptosis induction was detected in 5637 and EJ138 cells with no significant effect on HFFF cell. CONCLUSION: To our knowledge, this is for the first time reporting surface expression of FMOD in bladder cancer. This significant surface expression of FMOD in bladder cancer with no expression in normal bladder tissues and the capacity of inducing apoptosis through directed targeting of FMOD with specific monoclonal antibody might candidates FMOD as a diagnostic marker as well as a potential immunotargeting with monoclonal antibody.	bladder
Single Umbilical Stoma for Bilateral Ureterostomy after Radical Cystectomy.	PURPOSE: Cutaneous ureterostomy after radical cystectomy is less preferred compared with other permanent urinary diversions due to bilateral stomas. Single umbilical stoma for bilateral ureterostomy (SUSBU) may be a choice, in this study we reviewed the outcomes of SUSBU in seventeen patients who underwent radical cystectomy. METHODS AND MATERIALS: This was a case-series study conducted from April 2016 to Dec 2017. Seventeen male patients with confirmed PT2 bladder urothelial carcinoma who were not suitable for performing conduit or orthotopic urinary diversion, including those with high-risk patients underwent single umbilical stoma for bilateral ureterostomy after radical cystectomy. All patients were prospectively followed up for 24 months ± 2 months, this study was done in a teaching center mainly by senior residents. RESULTS: The mean age of patients was 68.6 ± 6.41 years. The mean length of operation time was 176.7 ± 15.1 minutes (from intubation to extubation from anesthesia). Sixteen patients were diagnosed with PT2 and one patient had a PT4 diagnosis. The decrease in hemoglobin level after surgery was 1.72 mg/dl ± 0.35 and creatinine increased by 0.15 ± 0.05 mg/dl. None of our patients had oliguria. One case developed constipation and no gas passing, with the suspicion of obstruction, underwent abdominal exploration, however, no obstruction or urine leakage was found and the patient was treated conservatively. One patient developed a fever during admission, in which atelectasis was identified as the cause. One patient underwent a second operation because of fascia dehiscence. CONCLUSION: It seems that this technique is suitable for high-risk patients with acceptable operating time, surgical complications, and fast recovery after the operation and one ureterostomy bag instead of two one's comparing to bilateral cutaneous ureterostomy.	bladder
Metastatic urothelial carcinoma to the brain, spinal cord and spine: A contemporary multi-institutional clinicopathologic analysis of 24 cases.	Only case reports and small series of metastatic urothelial carcinoma (UCa) to the central nervous system (CNS) or spine have been published. We identiﬁed 24 cases at our institutions. The mean patient age was 64 years (range: 41-78 years) with a male predominance. Nineteen (79%) cases involved the brain, 3 (13%) and 2 (8%) cases involved the spinal cord and spine, respectively. Most cases (79%) were a single mass with a mean size of 2.8 cm (range: 0.9-5.5 cm). With the exception of 3 cases demonstrating micropapillary UCa, all metastases showed morphologic features of conventional UCa. Prior to CNS and spinal metastases, there was a history of UCa involving only the bladder in 16 (67%) patients, ureter in 1 (4%) patient, and kidney/renal pelvis in 1 (4%) patient. In 1 additional patient (4%) each, the primary tumor involved both bladder and ureter, bladder and kidney/renal pelvis, and ureter and kidney/renal pelvis, respectively. Three (13%) patients had no known primary site. In two patients, the diagnosis of primary UCa was made concurrently as the CNS metastasis, and ranged up to 30 years in other patients. Follow-up was available in 14 patients with a mean duration of 7 months (range: 0-23 months), and 4 patients died of disease. Both clinicians and pathologists should be aware that concurrent or late CNS or spine metastases may occur and could present as a solitary mass even over a decade after the initial diagnosis.	bladder
Combination therapy with paclitaxel and gemcitabine after platinum-based chemotherapy in patients with advanced urothelial cancer.	OBJECTIVES: To evaluate the efficacy and tolerability of paclitaxel and gemcitabine therapy after platinum-based chemotherapy for patients with advanced urothelial carcinoma. METHODS: Consecutive patients with advanced urothelial carcinoma who received paclitaxel and gemcitabine therapy from December 2003 to March 2018 were retrospectively reviewed. The objective response for paclitaxel and gemcitabine therapy, progression-free survival and overall survival, and adverse events were evaluated. The reduction rate among each metastatic site and the associations between the clinical parameters and overall survival or progression-free survival were also assessed. RESULTS: We enrolled 58 patients. Complete and partial responses were observed in two (3.4%) and 15 patients (26%), respectively. The median progression-free survival and overall survival were 4.3 months (95% confidence interval 2.9-5.2) and 11.5 months (95% confidence interval 7.7-14.8), respectively. The objective response rates of primary site and metastases in lymph nodes, lung, bone, and liver were 6.0%, 37%, 23%, 0%, and 22%, respectively. Poor performance status (≥1), prior use of gemcitabine and the number of metastatic sites (≥2) were significantly associated with poor overall survival. Although three patients discontinued the treatment because of adverse events, there was no therapy-related death. CONCLUSIONS: Paclitaxel and gemcitabine therapy seems to be a valid option as a subsequent treatment after platinum-based chemotherapy for urothelial carcinoma, especially in patients with favorable performance status and no prior use of gemcitabine.	bladder
Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: A Medicare claims database analysis.	BACKGROUND: Several programmed death-1 or death-ligand 1 (PD-1/L1) inhibitors are approved first- or second-line therapies for locally advanced or metastatic urothelial carcinoma (la/mUC); however, clinical trials show that only ∼20% of patients respond and all ultimately progress. This study elucidated real-world treatment patterns, healthcare resource utilization (HRU), and economic burden among Medicare beneficiaries with la/mUC who discontinue PD-1/L1 inhibitor therapies. METHODS: We conducted a retrospective claims analysis of patients aged ≥65 years diagnosed with la/mUC (2015-2017) who initiated and subsequently discontinued PD-1/L1 inhibitor therapy (index=date of last administration) using Medicare Fee-for-Service Research Identifiable Files. Included patients had ≥12 months pre- and ≥3 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or data cutoff. RESULTS: Among 28,063 patients, 17% (n=4652) received ≥1 PD-1/L1 inhibitor following la/mUC diagnosis. Of these, 791 discontinued PD-1/L1 inhibitor therapy and met inclusion criteria (study cohort); 73% male, median age 76 years. Post-discontinuation, 3% received a different PD-1/L1 inhibitor, 46% chemotherapy, and 51% no further systemic treatment. HRU was high during follow-up: 97% had ≥1 outpatient visit and 52% ≥1 hospitalization. Healthcare costs per-patient-per-month were $7153 pre- and $7745 (adjusted) post-index; systemic therapy costs were higher pre- vs. post-index ($2978 vs. $1195) but other costs were higher post-index: hospitalization ($1120 vs. $2200), outpatient ($1437 vs. $2064), hospice ($3 vs. $536), skilled nursing facility ($106 vs. $384). CONCLUSIONS: Over half of Medicare beneficiaries with la/mUC received no disease-directed therapy post-PD-1/L1 inhibitor treatment. Patients who discontinued PD-1/L1 inhibitor therapy had intensive HRU unrelated to therapy costs, highlighting the significant burden of la/mUC and need for treatments that extend survival.	bladder
Incidental diagnosis of nonfunctional bladder paraganglioma: a case report and literature review.	BACKGROUND: Nonfunctional bladder paragangliomas is a rare urological disease. It may present clinical, radiology and pathological features similar to bladder cancer, Only scarce reports have been reported. Urologist must identify this generally benign neuroendocrine neoplasm to avoid misdiagnosis. CASE PRESENTATION: A 62-year-old female presented the outpatient department of our hospital with the symptoms of stomachache, frequent micturition, and urination pain for 20 days. Diagnosed with high blood pressure 1 year ago, administered Amlodipine besylate tablets 5 mg po qd occasionally, did not check blood pressure; denied any tumor observation in the family history. Color ultrasound of the urinary system showed a 38 mm × 34 mm hypoechoic mass on the right side of the bladder, CDFI: in the masses, blood supply was sufficient. Cystoscope showed bladder occupying lesion. Biopsy diagnosis: papillary polypoid cystitis was suspected as a malignant change (Fig. 3a). Then, the patient was admitted to our urological department. Further, computer tomography urography considered bladder cancer. Cystoscopy and biopsy failed to define the nature of the lesions in our outpatient department, which prompted a transurethral resection of the bladder tumor. histopathological and immunohistochemical results were diagnosed as bladder paragangliomas. For the reason, the tumor was removed by partial resection of the bladder. The postoperative recovery and follow-up were uneventful. CONCLUSIONS: Nonfunctional bladder paragangliomas are occasionally found on imaging studies with the symptoms of urinary tract infection or/and intermittent painless hematuria. It may present clinical, radiology and pathological features similar to bladder cancer, so knowledge of this generally benign neuroendocrine neoplasm is of great importance to avoid misdiagnosis. It should be accompanied by the clinical and pathological characteristics of the patient and image changes. Partial resection of the bladder can effectively treat this disease.	bladder
A Calibrated Multiexit Neural Network for Detecting Urothelial Cancer Cells.	Deep convolutional networks have become a powerful tool for medical imaging diagnostic. In pathology, most efforts have been focused in the subfield of histology, while cytopathology (which studies diagnostic tools at the cellular level) remains underexplored. In this paper, we propose a novel deep learning model for cancer detection from urinary cytopathology screening images. We leverage recent ideas from the field of multioutput neural networks to provide a model that can efficiently train even on small-scale datasets, such as those typically found in real-world scenarios. Additionally, we argue that calibration (i.e., providing confidence levels that are aligned with the ground truth probability of an event) has been a major shortcoming of prior works, and we experiment a number of techniques to provide a well-calibrated model. We evaluate the proposed algorithm on a novel dataset, and we show that the combination of focal loss, multiple outputs, and temperature scaling provides a model that is significantly more accurate and calibrated than a baseline deep convolutional network.	bladder
Activation of the DDR Pathway Leads to the Down-Regulation of the TGFβ Pathway and a Better Response to ICIs in Patients With Metastatic Urothelial Carcinoma.	Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of metastatic urothelial carcinoma (mUC), a dominant type of bladder cancer (BC). Previous studies have shown an association between gene mutations in the DNA damage response (DDR) pathway and the immunotherapy response in mUC but have neglected the effect of the activation level of the DDR pathway on the ICI response in mUC. A published immunotherapy cohort with genome, transcriptome and survival data for 348 mUC patients was used. An external cohort (The Cancer Genome Atlas Bladder Cancer) and the GSE78220 cohort were used for validation. The activation level of the DDR pathway was quantified using single-sample gene set enrichment analysis (ssGSEA). Further analysis on the genome, immunogenicity, and the immune microenvironment was conducted using the DDR ssGSEA enrichment score-high (DSSH) group and the DDR ssGSEA enrichment score-low (DSSL) group. In the mUC cohorts, the DSSH group was associated with longer overall survival times (P=0.026; Hazard ratio=0.67; 95%CI: 0.46-0.95). The DSSH group was also associated with higher tumor mutation burden, neoantigen load, immune-activated cell patterns, and immune-related gene expression levels. The GSEA results indicated an immune activation state in DSSH group, which correlated with a down-regulation in the transforming growth factor β receptor signaling pathway. Our study suggests that the activation level of the DDR pathway may be a novel predictive marker for immunotherapy efficacy in patients with mUC.	bladder